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Biomedical subjects

J F Winchester

Publications and source records attributed to J F Winchester.

At least 73 records · Page 4Linked to original sources
PubMed1981

Clinical analgesic nephropathy.

Analgesic nephropathy is recognized worldwide, but the differences in incidence in various countries, or regions, remain unexplained. Analgesic compounds may cause both functional and structural renal damage. This damage may be related to depletion of glutathione and renal vasoconstriction (probably mediated through prostaglandin depletion) and to the fact that the concentrations of glutathione and prostaglandins and their metabolites in the kidneys are manyfold their concentrations in plasma. Most patients with analgesic nephropathy are middle-aged women with histories of peptic ulcer, anemia, psychiatric disorders, headaches, and arthralgias. Investigations often show pyuria, some bacteriuria, and impaired concentrating ability, as well as other abnormalities of tubular function; caliceal abnormalities on intravenous pyelography are also frequent. It is important to discover these patients; evidence exists that with cessation of drug ingestion, renal function may stabilize and, in some cases, may improve.

Analgesics↗
PubMed1981

Extracorporeal treatment of salicylate or acetaminophen poisoning--is there a role?

Hemodialysis or sorbent hemoperfusion has been used in the management of clinical overdose of salicylates or acetaminophen. Hemodialysis offers considerable benefit in severe salicylate poisoning and is preferred to hemoperfusion or peritoneal dialysis, since it more rapidly corrects acid-base and electrolyte abnormalities than does hemoperfusion, and since it is clearly more efficient than is peritoneal dialysis for the removal of salicylates. Charcoal hemoperfusion in animal studies and hemodialysis in man have been shown to accelerate acetaminophen elimination from the body. Hemodialysis and hemoperfusion are of questionable benefit in clinical acetaminophen overdose. However, our clinical experience to date with charcoal hemoperfusion in "late" acetaminophen overdose has been associated with a less notable increase in liver enzyme concentrations in comparison with results of retrospective studies of series of patients treated or not treated with sulfhydryl donors.

Acetaminophen↗
PubMed1980

iron-overload-associated myopathy in patients on maintenance haemodialysis: a histocompatibility-linked disorder.

Unexplained proximal muscle weakness developed in 10 patients on chronic maintenance haemodialysis. Proximal muscle biopsy in 7 patients disclosed iron deposition in muscle fibres and/or macrophages. All 10 patients had severe iron overload (serum-ferritin level > 1000 ng/ml). Since HLA-A3, B7, and B14 antigens are associated with idiopathic haemochromatosis and, therefore, are linked with alleles regulating iron metabolism, HLA type was reviewed in 61 haemodialysis patients, including the 10 myopathic patients. Serum-ferritin levels showed a significant correlation (p<0.001) with the presence of the HLA-antigens. Close relatives of these patients with HLA-antigen-associated iron-overload myopathy did not have raised serum-ferritin levels. Patients on maintenance haemodialysis who have inherited the "haemochromatosis alleles" thus have an increased risk of iron overload and muscle iron deposition.

Adult↗
PubMed1980

Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations.

A double-blind crossover comparison was made in 18 nonedematous hypertensive subjects with glomerular filtration rates exceeding 70 ml/min/1.73 m2 of the effects of 5 mg metolazone and 5 mg bendroflumethiazide on blood pressure and metabolic parameters. After a 4-wk run-in placebo period, patients received either metolazone or bendroflumethiazide for 6 wk in a crossover fashion with an intervening washout period of 4 wk. Metolazone induced a more sustained and greater blood pressure response than bendroflumethiazide. Changes in plasma potassium, urate, bicarbonate, renin, and angiotensin II occurred during treatment with both metolazone and bendroflumethiazide; the only significant difference, however, was in changes in plasma bicarbonate. Total body potassium (TBK), measured by whole-body monitor, did not fall outside the normal range with either metolazone or bendroflumethiazide, although metolazone induced a greater reduction in TBK (6.2 gm, 5.5% of TBK) than bendroflumethiazide (1.2 gm, 1.1% of TBK, p < 0.05). Our results suggest that metolazone is a more effective antihypertensive and induces similar but greater metabolic changes than bendroflumethiazide. The results of our comparison suggest that although changes in plasma potassium and TBK are minor, they are greater with metolazone, and potassium supplements may not be necessary in nonedematous hypertensive patients with normal renal function.

Adolescent↗
PubMed1980

Will hemoperfusion be useful for cancer chemotherapeutic drug removal?

One of the major problems in clinical cancer chemotherapy is the inability to safely administer full therapeutic doses of specific drugs in the face of dysfunction of an organ system controlling that drug's metabolism and excretion. Should efficient drug removal from blood be possible following full therapeutic doses and after tumor exposure, then theoretically, even in the presence of organ dysfunction, anticancer drug toxicity may be reduced or avoided. Preliminary experiments in our laboratory have shown that adriamycin may be efficiently removed by activated charcoal from aqueous and protein solutions and blood in vivo, and that daunorubicin is removed in vitro to the same extent. However, although methotrexate is removed efficiently in vitro and extracted 50% in vivo by charcoal hemoperfusion, its overall pharmacokinetics do not appear to be altered in comparison with the alteration in pharmacokinetics of adriamycin achieved with charcoal hemoperfusion. Computer modeling has suggested that efficient adriamycin removal is achievable, and that clinical studies are warranted. For methotrexate removal, however, previous clinical studies and our own data suggest that charcoal hemoperfusion has little utility unless a highly specific sorbent for methotrexate removal can be developed.

Adsorption↗
PubMed1980

Pericardial effusion associated with minoxidil therapy in dialyzed patients.

Pericardial effusion, diagnosed clinically or by echocardiography, was found in 13 of 16 regularly dialyzed patients (81%) receiving minoxidil for refractory hypertension. In a comparable group of 125 patients not receiving minoxidil, 28 patients (23%) had evidence of pericardial effusion, the difference between the groups being highly significant (p less than 0.0005). In minoxidil treated patients, the effusions resolved spontaneously in 4 (3 remaining on treatment), required pericardiocentesis (3), or pericardiectomy (1), and persisted in 4 (3 remaining on treatment). It is suggested that minoxidil treated dialysis patients be regulary examined for the development of potentially threatening pericardial effusions.

Adult↗
PubMed1978

Solute, amino acid, and hormone changes with coated charcoal hemoperfusion in uremia.

This investigation assesses the effect of two-hour activated charcoal hemoperfusion using a column containing 300 g of acrylic hydrogel-coated activated charcoal either alone or combined with hemodialysis on small and "middle molecule" removal in uremic patients. Comparison was made with standard five-hour hemodialysis. Two patients with dialysis encephalopathy were treated with four-hour combined hemoperfusion/hemodialysis without beneficial clinical effects. Hemoperfusion increased the clearance rates of creatinine and urate when combined with dialysis. Hemoperfusion alone removed 1.3 +/- 0.6 g (mean +/- SD) of creatinine and 0.6 +/- 0.2 g of urate, while combined hemoperfusion/hemodialysis removed 1.7 +/- 0.6 g of creatinine and 1.0 +/- 0.5 g of urate in a two-hour period. Both treatment schedules removed less solute than standard five-hour hemodialysis but were associated with comparable "middle molecule" removal. Hemoperfusion accounted for additional amino acid removal when combined with hemodialysis, while hemoperfusion alone produced significant reduction only in the amino acid cystine. Changes in the hormones thyroxine, triiodothyronine, human growth hormone, and insulin were noted during the procedures. Acceptable falls in platelet counts and fibrinogen occurred with hemoperfusion. Coated charcoal hemoperfusion may prove to have a role in the management of uremic patients, although the acrylic hydrogel-coated charcoal hemoperfusion device requires combination with techniques allowing fluid and electrolyte removal.

Amino Acids↗